Peptides are transported in and out of human cells by several different transport mechanisms. One influx peptide transporter has been located in the brush border of the epithelial cells of the intestinal mucosa. Properties of this intestinal transporter (hereinafter "influx peptide transporter") have been studied in situ in intestinal mucosa preparations and in vitro with brush border membrane vesicles, isolated enterocytes, and cell culture.
Many different solutes, including small peptides, antibiotics, oral angiotension converting enzyme (ACE) inhibitors, and oral renin inhibitors are transported into the cytoplasm of the enterocyte by the influx peptide transporter. (e.g., Ganapathy and Leibach, 1991, Curr. Biol. 3:695-701; Okano et al., 1986, J. Biol. Chem. 261:14130-14134; Nakashima et al., 1984, Biochem. Pharm. 33:3345-3352). The influx peptide transporter plays a pivotal role in the absorption of certain oral drugs, including .beta.-lactams and ACE inhibitors. Out of 27 .beta.-lactam antibiotics examined, the influx peptide transporter was able to distinguish between those that are orally absorbed in humans and those that are not (Tabas et al., 1991, 31st Interscience Conference on Antimicrobial Agents and Chemotherapy Abstract No. 164). Moreover, the influx peptide transporter has been demonstrated to transport a number of oral .beta.-lactam antibiotics but not parenteral .beta.-lactam antibiotics in studies using human intestinal Caco-2 cells and rabbit intestinal brush-border membranes (Dantzig et al., 1992, Biochim, Biophys. Acta 1112:167-173; Dantzig et al., 1992, 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Anaheim, Calif., Abstract No. 1460; Snyder et al., 1992, 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy Abstract No. 1461; Okano et al., 1986, J. Biol. Chem. 261:14130-14134.) Similar studies have been conducted to examine the ability of the influx peptide transporter to predict which ACE inhibitors are orally absorbed (Friedman and Amidon, 1989, Pharm. Res. 6:1043-1047).
Influx peptide transporter activity has been identified as a 127,000 dalton membrane protein from rabbit intestinal mucosa by photoaffinity labeling methods employing radiolabeled penicillin or a radiolabeled cephalexin analog (Kramer, 1987, Biochim. Biophys. Acta 905:65-74; Kramer et al., 1988, Biochem. Pharmacol. 37:247-2435). A purified 127,000 dalton protein from rabbit intestinal mucosa preparations reconstituted into liposomes resulted in binding and transport activities, and polyclonal antibodies to this putative transporter were prepared (Kramer et al., 1990, Biochim, Biophys. Acta 1030: 50-59). Monoclonal antibodies (MAbs) reactive with human influx peptide transporter have not been previously described.
Proteins that are expressed in discrete locations in the body can be used as markers to determine the origin of cells or tissues. For example, carcinoembryonic antigen is a protein situated only in the colon and is used as a marker for colon tumor cells (Shrively, 1985, Crit. Rev. Oncol. Heamatol. 2:355-399). MAbs raised to unique proteins, such as the human influx peptide transporter, can be used to identify tumors and metastases that originate from a tissue that expresses that antigen. This may be done as a diagnostic in the laboratory or may be used in vivo with an imaging agent.